Novel galenical system for active transport, method for preparation and use

ABSTRACT

The invention relates to a novel galenical system for taste masking, protecting an active substance, in particular in an acid medium, modulating releasing properties, masking mucous irritability and toxicity of certain active substances, for preparing aqueous forms which have a masked taste, are stable and pH independent. Said invention also relates, in particular to a galenical system which is embodied in the form of lipidic solid particles and strictly hydrophobic and devoid of water, surface active agents, emulsifiers, solvent traces and which is characterised in that it comprises at least one type of hydrophobic wax and at least one type of fatty non-neutralised acid.

This invention relates to a new galenic system for the protection of anactive constituent, particularly a medicine, against degradation duringtransit in the stomach following oral absorption.

The galenic system according to the invention also enables masking ofthe taste of an active constituent in the galenic system, if any,stabilisation of the said active constituent, modulation of the releaseproperties of the said active constituent, masking or mucosalirritability effects and toxicity of some active constituents.

The simplest and the most practical therapeutic administration path isoral. In France, this path is used for 75% of all medicines taken(Pharmacie galénique, A. Le Hir-Editions Masson). Galenic forms intendedto be taken orally are essentially in two forms, liquid and dry. Theyhave the enormous advantage that they do not require any medicaltreatment when taking medicine.

The pH of the stomach is between 2 and 6. The acid nature of the stomachenvironment can cause degradation of active constituents contained iningested compositions before they have reached the intestine, wheretheoretically they are absorbed through the intestinal mucous membraneto pass into the circulation. Such a deleterious stomach transit effectcould be contradictory to the objective, namely absorption of the saidactive constituent by the organism in the most efficient form for therequired effect. This disadvantage is particularly important forpharmaceutical compositions.

Therefore there is a need for an excipient for active constituentsingested orally, capable of assuring stomach transit for the said activeconstituent without degrading the said active constituent. This is oneof the purposes of this invention.

Other problems are well known, with galenic forms intended to be takenorally, particularly galenic forms for medical purposes. A recurrentproblem with these galenic forms is compliance.

Compliance is a capital factor that directly depends on the efficiencyof the therapeutic treatment. Compliance, or correct use of themedicine, is defined as being the action of following a medicaltreatment in accordance with the indications in the prescription;respecting the treatment duration, the number of times and the timesduring the day that the medicine is taken. A medicine may be inactive ornot very efficient if is not taken at a sufficient dose or sufficientlyfrequently. For intermittent disorders, failure of correct compliance ofthe treatment can only delay the cure and lead to relapses, sometimesresponsible for serious complications. Poor compliance in the case ofchronic diseases can cause irreversible damages.

The main difficulties encountered during oral administration varydepending on the presentation.

The disadvantages for dry forms, tablets, capsules, gelatine capsulesare deglutition and taste. Some populations such as the elderly,children and some persons with mental disorders must choose the liquidform.

It is very easy to take medicine in liquid form, but this form alwaysfaces the unsolved problems of concealing the taste and instability ofmany active constituents in the aqueous phase.

Another of the objectives of this invention is to propose a galenicsystem capable of efficiently concealing the taste.

Finally, regardless of the form, irritability, mucosal toxicity andgastro-toxicity problems are also encountered when taking some activeconstituents, particularly medicines such as anti-inflammatorymedicines.

Another purpose of this invention is to propose a galenic system capableof a delayed release of an active constituent, particularly so that itis not released into stomach during ingestion. This property requiresthe use of a galenic system stable in an acid medium, in other wordsresistant to an acid pH.

As mentioned in document PCT/US99/27981, page 2, line 4, methods used tominimise bad taste are varied, including the addition of sweeteners,aromas, effervescent formulation and coating technologies. Coatingtechniques provide the only means of concealing the taste, while otherapproaches attempt to make the nature of the preparation moreappetising. These coating techniques were also selected to prevent therelease of gastrotoxic active constituents into the stomach.

Coating techniques consist of putting a layer of isolating compounds,polymers and mixes into place around the active constituent to isolateit from the external environment. Many natural and synthetic polymercompounds have been used to build up this external layer. They includemainly cellulose derivatives such as hydroxypropylmethylcellulose(HPCM), ethylcellulose, carboxymethylcelluloses,hydroxypropylmethylcellulose phthalate or mixes of these products. Thistechnique has given interesting results for varying the release rate andfor gastroprotection, but those skilled in the art know that the tasteis not concealed satisfactorily and the formulation in water remainsunstable in time, which is incompatible with the preparation of aqueousforms such as syrups and suspensions.

Other polymers such as polyacrylate derivatives, amonio-methacrylatepolymers or methacrylate proposed by the RÔHM Company have been used, asdescribed in document FR 2795962 and WO 98/47493. A lot of work has beencarried out with starch and particularly polycarbophiles and Carbopol asdescribed in patent WO 02/092106.

These coating techniques are well known to those skilled in the art. Adistinction can be made between physical coating processes based onsprinkling of the coating solution in a turbine or in a fluidised bed asdescribed in patents WO 00/30617 and WO 02/092106 firstly, and secondlyphysicochemical coating based on coacervation or the separation ofphases as described in patent U.S. Pat. No. 3,341,416. All thesetechniques lead to setting up one or several external polymeric layerscovering a central particle composed of the pure active constituent or amix in the form of granules of active constituents with other supportmaterials as described in document EP 1194125 issued by the PrographarmCompany.

We have seen that it was impossible to conceal the taste and keepabsorption properties of the initial molecule at the same time.

Immediate release at the digestive tube depends on the use of adependent pH polymer very sensitive to a pH greater than 7 in the mouthcavity or the stomach, which requires the addition of acid into thefinal formulation.

These coating techniques have a number of disadvantages:

-   -   gastroprotection is not complete    -   the taste is not completely concealed and the taste of compounds        that are very bitter is still too unpleasant    -   release rates are modified    -   coating particles have a size of a few hundred microns and are        perceptible during absorption. In this case, rupture of the        particles can cause a bad taste    -   coating processes are complex, they include many steps and are        expensive.

These technologies are not compatible with preparation of syrups thatare stable in the long term.

Therefore these technologies are not fully satisfactory.

The inventors have demonstrated that, surprisingly and unexpectedly, theaddition of non-neutralised fatty acids to the compositions of solidlipidic particles prepared according to the process described in patentWO 99/65448 that can contain an active constituent, provides a means ofobtaining stable hydrophobic particles in the stomach and that arereleased only in the digestive tube, thus providing gastroprotection andcomplete concealing of the taste without modifying the releaseproperties of the active constituent.

Thus, this invention proposes a new galenic system enabling:

-   -   gastroprotection,    -   concealing the taste,    -   protection of the active constituent, particularly in an acid        environment,    -   the possibility of modulating release properties,    -   concealing of mucosal irritability effects and toxicity of some        active constituents,    -   the preparation of aqueous forms with a concealed taste, stable        and with independent pH.

The galenic system according to the invention is characterised in thatit is composed of a mix of hydrophobic compounds insoluble in water, inthat it is in solid form at ambient temperature and that it hasabsolutely no surfactant compounds, solvent residues or water that couldcause hydrolysis or oxidation reactions of an active constituentcontaining it. This galenic system has the capability of incorporatinghydrophilic, hydrophobic or mineral type compounds.

Thus, the purpose of the invention is a strictly hydrophobic galenicsystem in the form of solid lipidic particles, containing no water orsurfactants, or emulsifying agents or traces of solvents, characterisedin that it comprises at least one hydrophobic wax and at least onenon-neutralised fatty acid.

In the remainder of the text, the terms “galenic system”, “lipidicparticle” and even “droplet” or “lipidic droplet” will be understood ashaving the same meaning.

In one particular form of the invention, the galenic system is also talcfree.

According to another particular form of the invention, the lipidicparticles are solid at a temperature of up to 45° C. and preferably upto 37.5° C.

According to another particular form of the invention, the lipidicparticles are in spherical form.

A hydrophobic wax according to the invention means that the galenicsystem may be composed of one or several vegetal, animal or mineralwaxes, or a mix of one or several waxes and at least one non-amphiphilicoil.

The galenic system may also comprise at least one hydrophobic compoundcapable of adjusting the melting point and the physicochemicalproperties such as the hardness. Examples of hydrophobic compoundsinclude beeswax and palm oil.

An appropriate composition compatible in terms of toxicity,biocompatibility, non-immunogenicity and biodegradability withabsorption by mouth or any other administration method, should bechosen. In this case, the compounds will be chosen from among compoundsalready used for oral administration such as those defined in the GRASlist published by the Food and Drug Administration, such that theparticles formed maintain their incorporation, taste concealing andstabilisation properties for active constituents.

Thus according to the invention, the wax may be chosen from among anyknown wax compatible with the requirements of the invention. Inparticular, the wax may be chosen from among:

-   -   triglycerides and derivatives    -   palm oil    -   Carnauba wax,

Candellila wax

-   -   Alfa wax    -   cocoa butter    -   ozokerite    -   vegetal waxes such as olive wax, rice wax, hydrogenated jojoba        wax or absolute flower waxes    -   beeswaxes and modified beeswaxes.

According to one particular form of the invention, the wax may be a mixof waxes.

According to the invention, a wax or a mix of waxes with a melting pointof between 15° C. and 75° C., and preferably between 30° C. and 45° C.can be used.

According to the invention, the quantity of wax may be between 0.5% and99%, and preferably between 1% and 50%.

According to the invention, the non-neutralised fatty acid may be anynon-neutralised fatty acid compatible with the requirements of theinvention. The non-neutralised fatty acid may be chosen from among fattyacids with linear chains with between 4 and 18 carbon atoms, for examplesuch as myristic acid, lauric acid, palmitic acid or oleic acid.

According to one particular form of the invention, the non-neutralisedfatty acid may be composed of a mix of non-neutralised fatty acids.

According to the invention, the non-neutralised fatty acid may be usedwith a fatty acid content by mass of between 0.5% and 75% and preferablybetween 1% and 30%.

The galenic system according to the invention may also contain oily,pasty or solid additives, liposoluble or hydrosoluble activeingredients.

Other compounds can also be used, such as fatty alcohols with a highmolecular weight, preferably linear and saturated fatty acids with aneven number of carbon atoms between 12 and 30, acid and alcohol esterswith a high molecular weight and particularly esters of linear andsaturated acids with an even number of carbon atoms between 4 to 20, andlinear and saturated alcohols with an even number of carbon atomsbetween 14 and 32. In all cases, the mix obtained must be characterisedby a final melting point between 15° C. and 75° C., by the absence ofsurfactant compounds, a hydrophobic behaviour and non-wettability bywater. Apart from the waxes mentioned above, the composition accordingto the invention may contain an oil or a mix from among:

-   -   hydrophobic silicon oils with a viscosity between 5 and 9000        centistockes, cyclomethicones,    -   lipophile organofluoridic oils,    -   perhydrosqualene.

Other oily compounds such as oleic alcohol, lanoline, sunflower oil,palm oil, olive oil, fatty acids and fatty alcohols may be used, but theoily mix obtained must be characterised by a hydrophobic behaviour, alack of miscibility with water and a melting point between 15° C. and75° C., and preferably between 30° C. and 45° C.

Clays or oily dispersions of clays, phenyl silicon gums, starches andfatty body structuring agents, can be added into the composition toadjust the consistency.

A number of compounds such as mineral fillers can be added to thehydrophobic matrix of the galenic system, to modulate the density andplasticity. Talc and kaolin will advantageously be chosen for themineral compounds.

The size of lipidic particles according to the invention may be between0.5 microns and 1500 microns, and preferably between 10 microns and 250microns.

Lipidic particles according to the invention have the advantage thatthey can enable delayed release of an active constituent contained inthem, very good stability to an acid pH particularly in an acid aqueousformulation, thus enabling protection of the active constituent whenthey are in contact with an environment with an acid pH, for examplesuch as the gastric environment, and complete concealing of the taste.

Another purpose of the invention is a galenic system according to theinvention also comprising an active constituent.

In this description, the term active constituent is used to denote anysubstances that can be used in cosmetics, pharmacy, biotechnology, inthe veterinary field or in food. In particular, according to theinvention, the active constituent may be an active therapeutic substancethat can advantageously be administered to man or other animals todiagnose, cure, reduce, treat or prevent a disease.

According to the invention, the active constituent may be anyhydrophilic, hydrophobic or mineral compound.

According to the invention, the active constituent may be dissolved ordispersed in the galenic system.

Obviously, according to the invention, the active constituent may be amix of active constituents.

The active constituent may be chosen from among essential oils, aromas,pigments, fillers, colouring agents, enzymes and coenzymes and otheractive substances.

Active constituents that may be incorporated into the galenic systemaccording to the invention include vitamins or provitamins A, B, C, D,E, PP and their esters, carotenoids, anti-radical substances,hydroxyacids, antiseptics, and molecules acting on the pigmentation,inflammation, biological extracts.

The active constituent may also be chosen from among preservatives,antioxidants, colouring agents and pigments, cells and cellularorganites or pharmaceutical compounds intended for the treatment ofpathologies, particularly skin or mucosal pathologies.

Examples of therapeutic active constituents that could be incorporatedinto the galenic system according to the invention include antibiotics,antifungicides, antiparasites, anti-malaria agents, adsorbents, hormonesand derivatives, nicotine, antihistamines, steroidal and non-steroidalanti-inflammatory agents, antiallergic agents, antalgics, localanaesthetics, antivirals, antibodies and molecules acting on theimmunitary system, cytostatics and anticancer agents, antalgics,hypolipemiants, vasodilators, vasoconstrictors, inhibitors of theangiotensin and phosphodiesterase conversion enzyme, nitrated andantianginal derivatives, beta-blocking agents, calcium inhibitors,antidiuretics and diuretics, bronchodilators, opiates and derivatives,barbiturates, benzodiazepines, molecules acting on the central nervoussystem, nucleic acids, peptides, anthracenic compounds, paraffin oil,polyethylene glycol, mineral salts, antispasmodic agents, gastricantisecretion agents, clay and polyvinylpyrrolidone gastriccytoprotectors, starch. This exhaustive list is in no way limitative.

According to the invention, the lipidic particles also comprise anactive constituent and have a melting temperature after the activeconstituent has been incorporated of between 15° C. and 75° C., andpreferably between 300 and 45° C.

The capacity of particles for holding an active constituent may varyfrom 0.02% to 75% by weight of the particles, and particularly from 5 to50%.

Those skilled in the art know that when these active constituents areincorporated into the galenic system, an appropriate lipidic compositionshould be chosen such that the particles are solid at the temperature ofuse with a size preferably between 0.5 microns and 1500 microns andpreferably between 0.5 microns and 100 microns, to completely concealthe taste without modifying the release properties and with very goodstability in an aqueous formulation even at a high pH. It is alsonecessary that the process for preparation of the said galenic systemalso comprising an active constituent can be used.

According to the invention, the galenic system also comprising an activeconstituent may be prepared using the process described in patent WO99/65448.

According to this embodiment of the process, the particles are obtainedby mixing with moderate heating. More specifically, these compositionsare obtained by a process characterised by the fact that wax and oil aremixed at the melting temperature of the wax to obtain a mixcharacterised by a melting temperature less than the melting temperatureof the wax. The initial ratio between the wax and the oil may bemodulated so that the melting temperature of the final mix is less thanthe degradation temperature of the compound to be incorporated that ismost sensitive to heat. The final mix must be solid at the temperatureof use and in one of these preferred forms it must have a melting pointof 37.5° C. The mix is then cooled with appropriate stirring, to atemperature of more than 2° C. or 3° C. at its melting point, to enableinclusion of pharmaceutical active constituents. The mix is then formedto result in hydrophobic spherical particles called particles.

Compared with hot melting techniques, the process according to theinvention does not involve any emulsifying agents or amphiphilicproducts in the composition, to enable stable dispersion during thesolidification phase by cooling.

According to one particular embodiment of the process according to theinvention, when the active constituent has to be completely eliminatedfrom the surface of lipidic particles, the invention includes a step towash the said particles obtained with a washing mix including ethanol.In this case, the presence of ethanol in the washing mix is essential tothe process since ethanol enables complete washing of any activeconstituent residues that may be present on the surface of the lipidicparticles that could create an unpleasant taste.

Thus according to this particular embodiment of the process according tothe invention, the different compounds in the galenic system (includingwax and non-neutralised fatty acid) and the active constituent are mixedin a first step of the process. The mix is made hot at 2° C. or 3° C.above the melting point of the compound with the highest melting point.Those skilled in the art know that a stirring method appropriate to thedispersion of all compounds must be used.

Then in a second step, lipidic droplets are formed comprising the activeconstituent by dispersing the mix obtained in the first step in a gelprepared with a gelifying, shear thinning and non surface active agentwith which the said mix is not miscible, previously adjusted to the sametemperature, and with a concentration of gelifying agent between 0.1 g/land 30 g/l, and preferably between 0.2 g/l and 20 g/l sufficiently highto fix the dispersion.

It may be preferable to inject the composition within the gel, forexample through an orifice located at the base of a reaction vessel.Stirring must be continued throughout injection and has a characteristicof using a blade equipped with an anchor designed to disperse thecomposition and a second axial blade equipped with a three-vanedimpeller designed to for dispersion droplets with the required size.This final step is extremely fast because the droplets are obtained asthe composition is being injected. There is no need to maintain stirringafter the end of injection, because the droplets are fixed in the gel.

In a third step according to the process, the droplets are immediatelycooled to below this mix solidification temperature at the end of theinjection and are then washed.

The washing phase is very important because it makes it possible to nolonger have any residue on the surface of particles, which could createan unpleasant taste.

Thus, regardless of the form of embodiment of the process according tothe invention, particles may be washed using a washing mix composed ofwater and between 0% and 25% of ethanol.

Finally in a fourth step, the washed particles are then recovered bysieving and are then dried. The particles obtained have excellent sizehomogeneity and can be manipulated industrially with no specialprecautions.

Those skilled in the art know that other dispersion methods such assonication or static mixers can be used.

Therefore the process according to the invention is fast and does notrequire any long and difficult stirring step. It can incorporate theactive constituent into the galenic system during the first mixing stepof the different ingredients in the composition.

Examples of shear thinning and non-surface active gelifying agentsappropriate for formation of the gel used as the dispersion mediumaccording to the process, include carboxyvinyl polymers such aspolyacrylic polymers not modified by hydrophobic groups or surfactants,carrageenans, thickeners and polysaccharidic gels such as xanthenes,guar and carob gums, alginates, cellulose derivatives, pectins, agar ora mix of these products.

Lipidic particles comprising an active constituent may be incorporatedinto any composition, and particularly into any cosmetic,pharmaceutical, veterinary or food composition.

Another purpose of the invention is a composition comprising at leastone lipidic particle containing an active constituent.

The composition according to the invention may also include any additiveintended to modify the appearance or the rheology. For example,lubricants can be added to the dry powder of particles to improve theirfluidity, for example such as talc, starches, silica powders, antistaticagents. Obviously, the composition according to the invention may be inthe form of any appropriate galenic formulation. In one advantageousform of the production, the particles according to the invention areused in aqueous suspensions, syrups and sachets. Finally, the particlesmay be used in conventional galenic formulations such as capsules,gelatine capsules, granules, oral powders, dispersible powders, tablets,hydrodispersible and orodispersible tablets.

According to another aspect of the invention, the compositions may beused for administration by injection and particularly for thepreparation of forms with prolonged release. In this case, lipidicparticles according to the invention are prepared so that their size ispreferably between 0.5 μm and 5 μm. It is preferable to sieve them toobtain a size distribution conform with the mode of administration.Their waxy composition is chosen to be conform with the requirements forinjection. This galenic form can eliminate toxicity problems encounteredby polymeric particles obtained using polymerisation in emulsionprocesses, related to the use of solvents and surfactant compounds.

The particles according to the invention can be used to obtain contentsof the active constituent equal to between 0.10 and 2 grams/gram of waxymatrix. Those skilled in the art know that these contents cannot bereached using encapsulation technologies. Finally, particle degradationdoes not cause any inflammatory reaction like the reaction that canoccur with injectable particles based on a polylactic-glycolic polymer.

The following examples are not limitative and are simply used toillustrate the invention. Taste concealing tests for some of thefollowing examples were carried out with a sample of 10 individuals. Theresults are expressed on the following scale:

-   -   1: the taste of the active constituent is detected    -   2: the taste of the active constituent is perceived slightly    -   3: the taste of the active constituent is detected    -   4: the taste of the active constituent is still acceptable    -   5: the taste of the active constituent is not acceptable.

EXAMPLE 1 Particles Containing Erythromycin

Example given for the production of 120 g of particles containingerythromycin:

Composition: Palm oil 80 g  Oleic acid 5 g Stearic acid 4 g Trilaurin 1g Erythromycin 30 g 

namely 120 g of dry particles contain 30 g of erythromycin.

Operating Method:

The compound with the highest melting point in a thermostat controlledreceptacle is heated to 2° C. above its melting temperature, and thedifferent compounds are then added gradually, in order of their meltingpoint, from the highest melting point to the lowest melting point. Themix temperature is gradually reduced to be kept at 2° C. to 3° C. abovethe melting temperature of the new mix obtained. The erythromycine isadded last. These compounds are dispersed in the lipidic phase using astirring system equipped with a mobile in a form of an anchor at a speedof 200 rpm. When the mix is homogenous, it is added to 600 ml of aqueousgel with 0.2% of Ultrez 10 carbopol, neutralised to pH 6.5 with soda,previously adjusted to the same temperature as the lipidic mix andcontained in a reaction vessel equipped with a stirring system with athree-vaned impeller. The stirring speed of the three-vaned impeller is110 rpm during addition of the composition. Stirring is maintained for30 seconds after the composition has been added and is then stopped. Thedispersion is then cooled to 15° C. The particles are recovered by andthen washed with distilled water, then with a mix of distilled waterwith 15% of ethanol, and are then recovered and dried. The average sizeof the particles thus obtained is 62 microns. These particles have noactive constituent on their surface.

After extraction, the erythromycin on the particles is analysed by HPLC.29.3 g of erythromycin is obtained per 100 g of matrix.

It is well known that compositions containing erythromycin have s strongtaste. The active constituent was not detected during the taste testcarried out on the particles.

EXAMPLE 2 Preparation of a Syrup Containing Particles ContainingErythromycin

A pharmaceutical saccharose syrup distributed by the Cooper company andcalled Simple Syrup is used, with the following composition: Saccharose86.50 g Sodium methyl parahydroxybenzoate 0.15 g Sodium propylparahydroxybenzoate 0.03 g Pure water to make 100 ml

20 g of particles containing erythromycin obtained in example 1 areadded to 250 ml of syrup at ambient temperature, corresponding to 5.86 gof erythromycin. The active constituent was not detected during thetaste concealing test carried out on the syrup.

EXAMPLE 3 Preparation of a Powder for Hydrodispersible OralAdministration, Containing Particles Containing Erythromycin

The following are placed in a powder mixer: Particles according toexample 1 100 g  Aroma 7 g Aspartamine 3 g Xanthene gum 1 g

After mixing, the powder is distributed in 2.24 g individual sachetscontaining 500 mg of erythromycin. An aqueous dispersion of theantibiotic is reconstituted by dissolution in 50 ml water. The activeconstituent was not detected during the taste test carried out on thedispersion.

EXAMPLE 4 Particles Containing Paracetamol

Example given for the production of 100 g of particles to reduce thegastrotoxicity of paracetamol:

Composition: Palm oil 49.0 g  Oleic acid 20.0 g  Stearic acid 4.5 gCapric acid 1.0 g Behenic acid 0.5 g Paracetamol  25 g

The operating method is exactly the same as that described in example 1.

The active constituent was not detected during the taste concealing testcarried out on the particles.

EXAMPLE 5 Particles Containing Oxytetracycline

Example given for the preparation of 100 g of injectable particles withprolonged release and containing oxytetracycline:

Composition: Trilaurin 39 g Tricaprin 32 g Oleic acid  3 g Stearic acid 1 g Oxytetracycline 25 g

As mentioned in example 1, the particles were obtained by dispersion ofthe lipidic phase in the gelified aqueous phase while stirring. Theconcentration of carbopol in the aqueous phase is 0.05%. Stirring isdone using an axial turbo-stirring rod at a speed of 300 rpm, so as toreduce the average size of particles to 1 μm. Stirring is maintained for60 seconds after the end of addition of the composition and is thenstopped. The dispersion is then cooled to 15° C. The particles arerecovered by sieving and are then washed with distilled water, and thenby a mix of distilled water with 15% of ethanol, and are then recoveredand dried. The average size of the particles thus obtained is 1.2microns.

1. Galenic system in the form of strictly hydrophobic solid lipidicparticles containing no water, surfactants, emulsifying agents or tracesof solvents, characterised in that it comprises at least one hydrophobicwax and at least one non-neutralised fatty acid.
 2. Galenic systemaccording to claim 1, characterised in that it is solid at a temperatureof up to 45° C. and preferably up to 37.5° C.
 3. Galenic systemaccording to either of claims 1 or 2, characterised in that the lipidicparticles are in a spherical form.
 4. Galenic system according to anyone of claims 1 to 3, characterised in that the hydrophobic wax is avegetable, animal or mineral wax, or a mix of at least one wax and atleast one non-amphiphilic oil.
 5. Galenic system according to any one ofclaims 1 to 4, characterised in that quantity of wax is between 0.5% and99%, and preferably between 1% and 55%.
 6. Galenic system according toany one of claims 1 to 5, characterised in that it also comprises atleast one hydrophobic compound.
 7. Galenic system according to any oneof claims 1 to 6, characterised in that the melting point of the wax maybe between 15° C. and 75° C., and preferably between 30° C. and 45° C.8. Galenic system according to any one of claims 1 to 7, characterisedin that the wax is chosen from among triglycerides and derivatives, palmoil, Carnauba wax, Candellila wax, Alfa wax, cocoa butter, ozokerite,vegetable waxes such as olive wax, rice wax, hydrogenated jojoba wax orabsolute flower waxes, beeswaxes and modified beeswaxes.
 9. Galenicsystem according to any one of claims 1 to 8, characterised in that thenon-neutralised fatty acid is chosen from among fatty acids with linearchains with between 4 and 18 carbon atoms, for example such as myristicacid, lauric acid, palmitic acid or oleic acid.
 10. Galenic systemaccording to any one of claims 1 to 9, characterised in that the fattyacid has a content by mass of between 0.5% and 75% and preferablybetween 1% and 30%.
 11. Galenic system according to any one of claims 1to 10, characterised in that it is in the form of lipidic particles witha size of between 0.5 microns and 1500 microns, and preferably between10 microns and 250 microns.
 12. Galenic system according to any one ofclaims 1 to 11, characterised in that it also comprises an activeconstituent.
 13. Galenic system according to claim 12, characterised inthat it has a melting temperature between 15° C. and 75° C. andpreferably between 30° C. and 45° C., after incorporation of the activeconstituent.
 14. Galenic system according to either of claims 12 or 13,characterised in that the capacity of particles for holding an activeconstituent may vary from 0.02% to 75% by weight of the particles, andparticularly from 5 to 50%.
 15. Preparation process for the galenicsystem according to any one of claims 12 to 14, characterised in that ina first step, the wax and the non-neutralised fatty acid are mixed hot,while stirring, at 2° C. or 3° C. above the melting point of thecompound with the highest melting point, in a second step, lipidicdroplets comprising the active constituent are formed by dispersing themix obtained in the first step in a gel with which the said mix isimmiscible, previously adjusted to the same temperature as the mixobtained in the first step, and with a content of gelifying agentbetween 0.1 g/l and 30 g/l and preferably between 0.2 g/l and 20 g/l, ina third step, immediately at the end of injection, the droplets areimmediately cooled below the solidification temperature of the mix, thenwashed with water possibly containing ethanol, in a fourth step, thewashed particles are recovered by sieving and dried.
 16. Processaccording to claim 15, characterised in that in the washing mix iscomposed of between 0% and 25%, and preferably between 1% and 10%, ofethanol.
 17. Process according to either of claims 15 or 16, the gel isprepared with a shear thinning and non-surface active gelifying agentchosen among carboxyvinyl polymers such as polyacrylic polymers notmodified by hydrophobic groups or surfactants, carrageenans, thickenersand polysaccharidic gels such as xanthenes, guar and carob gums,alginates, cellulose derivatives, pectins, agar or a mix of theseproducts.
 18. Composition comprising at least one galenic systemcontaining an active constituent as described in any one of claims 12 to14.
 19. Composition according to claim 18, characterised in that it is acosmetic, pharmaceutical, veterinary or food composition. 20.Composition according to either of claims 18 or 19, to be used for oraladministration or by injection.